Tox In Focus

Focused Clinical Reference

Vol. 24 · Opioids · July 2026

Drug Quick Reference

Drug Class / Mechanism

Mu-opioid receptor agonists

Natural, semi-synthetic, and synthetic

Street Names

Varies by agent

Diverted or illicit

Routes of Administration

Oral, injection, insufflation

Transdermal (some agents)

Commonly Detected With

Benzodiazepines, stimulants · Fentanyl (illicit supply)

Metabolism

Phase 1 CYP3A4/2D6; phase 2 UGT2B7

Many parents convert to active opioids

Window of Detection

Urine ~1 to 4 days

Oral fluid ~24 to 48 h

Control Status

DEA Schedule II-V (varies by agent)

OPIOIDS

Parent-metabolite relationships, poppy seed, and why the opiate screen misses synthetics

The opiate immunoassay is a class screen calibrated to morphine and codeine; it detects some semi-synthetic opioids at higher concentrations but misses synthetics such as fentanyl, methadone, and tapentadol. LC-MS/MS identifies specific opioids and their metabolites, which is essential because many opioids metabolize into other opioids that are themselves test targets.¹

Why This Matters Now

Interpreting an opioid panel requires knowing the metabolic relationships: codeine converts to morphine, hydrocodone to hydromorphone, and oxycodone to oxymorphone, so a positive metabolite can reflect the parent drug rather than separate use. Misreading these relationships can wrongly suggest non-prescribed use.²

⚠ Before flagging an unexpected opioid, check whether it is a known metabolite of the prescribed drug (see the metabolism grid). Poppy seeds and prescription sources can also explain morphine or codeine positives.

Clinical Presentation

INTOXICATION

Analgesia, euphoria, sedation

Miosis

Respiratory depression

Nausea, vomiting

Constipation (persists with tolerance)

WITHDRAWAL

Anxiety, agitation

Myalgia, GI upset

Rhinorrhea, lacrimation

Yawning, piloerection

Craving

Important: Opioid interpretation hinges on parent-metabolite relationships and CYP genetics. A detected opioid may be a metabolite of the prescribed drug, not evidence of additional use; conversely, absence of an expected metabolite can reflect altered CYP2D6 metabolism.

UDT Considerations

LC-MS/MS distinguishes specific opioids and metabolites that immunoassay cannot. Key phase-1 relationships (codeine to morphine, hydrocodone to hydromorphone, oxycodone to oxymorphone) mean a metabolite can appear without separate use of that drug.³ Poppy seed ingestion can produce morphine (rarely over 3,000 ng/mL in urine) and codeine, so consider diet before concluding illicit use.⁴

Clinical Guidance

Do not rely on an opiate immunoassay to detect fentanyl, methadone, or tapentadol; order specific LC-MS/MS.¹
Interpret unexpected opioids against the parent-metabolite grid before concluding non-prescribed use.³
Consider poppy seed, prescription sources, and heroin for morphine or codeine positives.⁴
Account for CYP2D6 and CYP3A4 variation and interactions that alter metabolite ratios.³
Correlate results with the prescribed regimen and clinical picture.

Point-of-Care Testing Availability

Available strips

The opiate immunoassay detects morphine and codeine, and hydrocodone at higher levels.

Clinical use

It does not reliably detect synthetic opioids such as fentanyl, methadone, or tapentadol.

Limitations

LC-MS/MS identifies specific opioids and their metabolites.

OPIOIDS | Clinical & Program Guidance

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Interpreting the Test Result

▲ If Testing Is Positive

Identify the specific opioid. LC-MS/MS names the opioid and metabolite; the opiate screen only flags the class.

Metabolite may equal the parent. A detected opioid can be a metabolite of the prescribed drug, not additional use.³

Consider diet and source. Poppy seed, prescription morphine or codeine, or heroin can explain morphine/codeine.⁴

▼ If Testing Is Negative or Not Done

Screen misses synthetics. A negative opiate immunoassay does not exclude fentanyl, methadone, or tapentadol.

Timing and cutoff. Absence may reflect timing of last use, dose, or levels below the cutoff.

Metabolism varies. Altered CYP activity can shift which analytes appear.

Parent Opioid and Phase-1 Metabolites

Opioid	Phase-1 metabolite(s)
Codeine	Morphine (and minor hydrocodone)
Hydrocodone	Hydromorphone, norhydrocodone
Oxycodone	Oxymorphone, noroxycodone
Morphine; hydromorphone; oxymorphone	None (parent compounds)
Fentanyl	Norfentanyl
Methadone	EDDP
Tramadol	O-desmethyltramadol, N-desmethyltramadol
Buprenorphine	Norbuprenorphine

A detected metabolite can reflect the parent drug, not separate use; CYP2D6 and CYP3A4 variation shifts these ratios.

Key References

Center for Substance Abuse Treatment. Clinical drug testing in primary care. TAP Series 32. SAMHSA; 2012.
Smith HS. Opioid metabolism. Mayo Clin Proc. 2009;84(7):613-624.
Trescot AM, et al. Opioid pharmacology. Pain Physician. 2008;11:S133-S153.
Concheiro M, et al. Morphine and codeine in oral fluid after controlled poppy seed administration. Drug Test Anal. 2015;7(7):586-591.

DISCLAIMER: This document is intended for clinical reference and educational purposes only. It does not constitute medical, legal, or professional advice and should not replace independent clinical or programmatic judgment. Content reflects published data available at time of preparation. ToxiPharm LLC makes no warranties regarding completeness or applicability in all settings. | © 2026 ToxiPharm LLC | toxipharm.org